Biomedical subjects
M A Pathak
Publications and source records attributed to M A Pathak.
Induction of mixed-function oxidases in mouse liver by psoralens.
8-methoxypsoralen, the most widely used psoralen in photochemotherapy, was shown to induce mixed-function oxidases. Induction of mixed-function oxidases in mouse liver was examined after mice were given a single dose of one of three psoralens. 8-methoxypsoralen clearly induced p-nitroanisole O-demethylase and slightly induced aryl hydrocarbon hydroxylase. Psoralen and 4,5',8-trimethylpsoralen failed to induce either enzyme. These results represent the first enzyme induction studies on these clinically useful compounds. The studies may have relevance in understanding the clinical differences in skin photosensitizing activity and photochemotherapeutic effectiveness of the compounds in such diseases as psoriasis and vitiligo.
Beta carotene therapy for erythropoietic protoporphyria and other photosensitivity diseases.
We treated with high doses of oral beta carotene (Solatene) (15 to 180 mg/day) 133 patients suffering from erythropoietic protoporphyria (EPP), 27 patients with polymorphous light eruption, six patients with solar urticaria, three patients with hydroa aestivale, one patient with porphyria cutanea tarda, and two patients with actinic reticuloid to relieve the photosensitivity associated with these diseases. Eighty-four percent of the patients with erythropoietic protoporphyria increased by a factor of 3 or more their ability to tolerate sunlight. On the other hand, only nine of the patients with polymorphous light eruption, and one fifth of the patients with all of the other forms of photosensitivity treated showed similar improvement. We conclude that beta carotene is an effective treatment for EPP, but that other forms of photosensitivity will need empirical therapeutic study with beta carotene to determine the range of effectiveness, if any, of this compound in conditions other than EPP.
Photochemotherapy: identification of a metabolite of 4, 5', 8-trimethylpsoralen.
A compound, 4, 8-dimethyl, 5'-carboxypsoralen (DMeCP), has been identified in mouse urine as a major metabolite of the photoactive drug, 4, 5', 8-trimethylpsoralen (TMeP). This drug is widely used in the treatment of vitiligo and psoriasis. DMeCP is fluorescent, and nonphotosensitizing when tested on guinea pig skin. DMeCP also occurs in the urine of human patients receiving TMeP orally.
Photochemotherapy of vitiligo. Use of orally administered psoralens and a high-intensity long-wave ultraviolet light system.
A new light source that provides high-intensity ultraviolet light (UVA) (300 to 400 nm) to the entire body surface makes orally administered psoralen treatment of vitilligo with an artificial light practical. In the 26 patients studied, the degree of repigmentation with either trioxsalen (TMP) or methoxsalen (8-MOP) and high intensity UVA was at least as great as that with the same oral agents and sunlight. With artificial UVA and similar treatment conditions, the two psoralen derivatives were compared in the treatment of vitiligo; TMP stimulated repigmentation as well as 8-MOP and caused fewer side effects.
Molecular and genetic basis of furocoumarin reactions.
Explore the source record for details and available documents.
Cutaneous effects of pulsed nitrogen gas laser irradiation.
The effects of pulsed nitrogen gas laser emission (337.1 nm wavelength) were studied on human skin. The laser provides high-intensity monochromatic UVA radiation and can elicit delayed erythema in an actual exposure time of about 1 msec (105,000 pulses, each lasting 10 nsec, delivered over 210 sec). The effects of nitrogen laser irradiation were compared clinically and histologically with conventional erythemogenic UVA and UVB exposures from xenon arc or mercury arc lamps and were found to be similar in many respects. The minimal erythema dose is comparable to that obtained using more conventional continuous light sources which have more than 100 times lower intensity. A phototoxicity comparison of oral and topically applied psoralens is presented, indicating that the laser may prove useful in comparing photosenitizing capacity of certain compounds.
Prolonged ultraviolet light-induced erythema and the cutaneous carcinoma phenotype.
A considerable amount of evidence exists in support of the role of ultraviolet radiation as a major etiologic factor in human skin cancer, both melanoma and carcinoma types. On the basis of epidemiologic studies a phenotype has been described which helps to identify the persons who are more susceptible to skin cancer. In an attempt to further define this population, patients with cutaneous carcinoma and a normal control group were exposed to artificial ultraviolet light (UVL) and the erythema and tanning responses of each group were measured over a 21-day period. UVL-induced erythema was prolonged in a significantly higher percentage of patients with skin cancer than in control patients, lasting two to three weeks after single exposures to 6 and 8 times the patient's minimal erythema dose. The presence of prolonged erythema correlated with this history of previous skin cancer but did not correlate with other established risk factors for cutaneous carcinoma, i.e., fair skin, light hair and light eyes, easy sunburning and poor tanning, and Celtic ancestry. Prolonged erythema following UVL radiation may therefore represent an additional risk factor and help to identify the skin cancer-susceptible population.
Photochemotherapy for psoriasis with orally administered methoxsalen.
Photochemotherapy denotes a therapeutic approach that is based on the interaction of light and a photoactive drug. This study describes the efficacy of photochemotherapy, using orally administered methoxsalen and long-wave ultraviolet light in 91 patients with severe, generalized psoriasis. Oral administration of methoxsalen was followed by exposure to a high-intensity long-wave ultraviolet light source, emitting a continuous spectrum between 320 and 390 nm (peak, 365 nm) and an energy of 5.6 to 7.5 mw/sq cm at 15 cm. There was complete clearing of 82 patients (90%), a 90% to 100% clearing in seven (8%), and a satisfactory improvement in two (2%). A paired comparison study in 54 patients showed photochemotherapy to be far more effective than ultraviolet light emitted by fluorescent bulbs or a xenon source. Eighty-five percent of the patients receiving outpatient maintenance treatment have remained in remission for periods up to 400 days.
[Photochemotherapy of psoriasis].
Explore the source record for details and available documents.
Letter: Porphyria cutanea tarda in young women.
Explore the source record for details and available documents.
Letter: Facial irritation due to sunscreen products.
Explore the source record for details and available documents.
Role of light in human skin color viariation.
The major source of color in human skin derives from the presence within the epidermis of specialized melanin-bearing organelles, the melanosomes. Tanning of human skin on exposure to ultraviolet light results from increased amounts of melanin within the epidermis. Melanosomes synthesized by melanocytes are acquired by keratinocytes and transported within them to the epidermal surface. In some cases, the melanosomes are catobolized en route. New information indicates that the multicellular epidermal melanin unit (melanocyte and associated pool of keratinocytes) rather than the melanocyte alone is the focal point for the control of melanin metabolism within mammalian epidermis. Gross human skin color derives from the visual impact of the summed melanin pigmentation of the many epidermal melanin units. In theory, constitutive skin color in man designates the genetically-determined levels of melanin pigmentation developed in the absence of exposure to solar radiation or other environmental influences; facultative skin color or "tan" characterizes the increases in melanin pigmentation above the constitutive level induced by ultraviolet light. The details of genetic regulation of pigment metabolism within the epidermal melanin units are being clarified. In some mammals at least, the function of epidermal melanin units is significantly influenced by hormones which may be regulated by radiations received through the eyes. Based on an evolutionary history of the human family which exceeds ten million years, it is proposed that melanin pigmentation may have played a number of roles in human adaptions to changing biologic and physical environments.
The detection of carotenoid pigments in human skin.
Carotenoid pigments were extracted chemically from both epidermis and dermis obtained from non-carotenemic individuals at autopsy. Absorption maxima characteristic of beta-carotene were found in the extracts of specimens of epidermis following cantharidin application in volunteers made carotenemic by the ingestion of beta-carotene (180 mg/day for 10 weeks). These maxima were absent in the extracts of epidermis obtained from the volunteers before beta-carotene ingestion.
Phytoene as a protective agent against sunburn (greater than 280 nm) radiation in guinea pigs.
Explore the source record for details and available documents.
Letter: Ultraviolet light therapy for psoriasis.
Explore the source record for details and available documents.
Tar photoxicity and phototherapy for psoriasis.
The photoxicity of coal tars was determined by comparing the ultraviolet light (UVL) energy required to produce erythema at tar treated sites (minimal phototoxic dose [MPD]) with the energy required to produce the same degree of erythema at untreated control sites (minimal erythema dose [MED]). The ratio of MED/MPD is the photoxic index (PI). Tars that were phototoxic had a PI of greater than 1. Using a UVA (320 to 400 nm) and a tuvb (290 to 320 nm) light source, 15 subjects and six tars were tested. All tars were phototoxic to UVA but not to UVB (P smaller than 0.0001). Although tar and UVL is a widely accepted treatment for psoriasis (Goeckerman therapy), the light sources employed at normal exposure times provide insufficient UVA energy to produce a phototoxic reaction to the tars are used. The therapeutic response seen in psoriatic patients treated with tar and UVL should therefore not be attributed to tar phototoxicity.
Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light.
Explore the source record for details and available documents.